Acoustic Separator for Low-Cell Flow Cytometry

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Solution Overview

Problem

Current methods for processing biological samples for flow cytometry are laborious and often damage cells, requiring centrifugation and purification steps that can lead to cell loss and reduced viability.

Innovation Solution

A method involving contacting a biological sample with an assay reagent containing analyte-specific binding members, followed by introduction into a flow cytometer with an integrated acoustic separator, which acoustically separates and concentrates cells without the need for traditional washing or centrifugation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If traditional centrifugation and purification protocols are used, then cell separation and concentration are achieved, but cell viability is reduced and cell loss occurs

Engineering Contradiction:

Improvecell separation qualityVSAvoidcell viability

Core Design Contradiction:

Manufacturing precisionVSReliability

Solution Approach 1:

The patent replaces the mechanical centrifugation system with an acoustic field-based separation system. Acoustic radiation pressure and acoustic streaming effects are used to separate and concentrate cells without mechanical forces, thereby maintaining cell viability while achieving effective cell separation and concentration.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the physical parameters of the fluid medium by adjusting viscosity and flow rate to optimize acoustic separation efficiency. By controlling these parameters, the system achieves effective cell separation without requiring harsh purification protocols that would damage cells.

Inventive Principle:

Principle #35Parameter changes

2Manufacturing precision

If traditional washing and concentration steps are performed, then sample purity is improved, but processing time increases and cell damage occurs

Engineering Contradiction:

Improvesample purityVSAvoidprocessing time

Core Design Contradiction:

Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent merges multiple traditional processing steps (washing, concentration, and separation) into a single integrated acoustic separation process. This consolidation eliminates intermediate transfer steps and reduces overall processing time while maintaining sample purity through continuous acoustic field-based separation.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The acoustic separation process operates continuously without interruption, maintaining constant acoustic fields that continuously separate and concentrate cells as they flow through the device. This continuous action eliminates the start-stop nature of traditional batch processing, reducing total processing time while maintaining purity.

Inventive Principle:

Principle #20Continuity of useful action

3Quantity of substance

If manual centrifugation and purification steps are used, then cell concentration is achieved, but labor intensity increases and cell aggregation occurs

Engineering Contradiction:

Improvecell concentrationVSAvoidoperational simplicity

Core Design Contradiction:

Quantity of substanceVSEase of operation

Solution Approach 1:

The acoustic separation system automatically performs cell concentration without requiring manual intervention for each processing step. The acoustic fields self-organize to separate and concentrate cells based on their physical properties, eliminating the need for operator-performed centrifugation and purification steps while preventing cell aggregation through controlled acoustic streaming.

Inventive Principle:

Principle #25Self-service

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach allows for efficient processing and analysis of biological samples with minimal cell loss and improved viability, enabling direct analysis of the sample assay composition without intermediate purification steps.

Implementation Method 1

an acoustic field generator positioned adjacent to the flow channel and configured to produce an acoustic field in the flow channel

Methodology Applied

Scientific EffectAcoustic radiation pressure: Acoustic Radiation Pressure

Implementation Method 2

acoustically separates and concentrates cells without the need for traditional washing or centrifugation

Methodology Applied

Scientific EffectAcoustic streaming:

Data Source

PatentUS12135272B2Multi-color flow cytometric analysis of samples with low cell numbers

Publication Date: 2024.11.05 BECTON DICKINSON & CO

AI summary

Aspects of the present disclosure include methods for processing a biological sample. Methods according to certain embodiments include contacting a biological sample having cells with an assay reagent that includes one or more analyte-specific binding members to produce a biological sample assay composition and introducing the biological assay composition into an inlet of a flow cytometer having an integrated acoustic separator. Systems, including a flow cytometer with integrated acoustic separator having one or more acoustic concentrator devices suitable for practicing the subject methods are also described.